tbuckley/cabot-search huggingface dataset:
Beneficial role of customized intraoral stents in radiotherapy for nasopharyngeal carcinoma.
Authors: Mi Yang, Huanhuan Xie, Zhen Hou, Yuya Jiang, Kongcheng Wang, Fangfang Sun, Juan Wang, Shuangshuang Li, Juan Liu, Shanbao Gao, Jing Yan
Journal: Journal of Clinical Oncology (2022)

e18642 Background: The intraoral stent is a mouth-opening device which may be used in nasopharyngeal carcinoma (NPC) patients during radiotherapy with the intention of preventing unnecessary irradiation in normal adjacent tissue. The purpose of this study was to investigate the effects of individualized intraoral stent on the intensity modulated radiation therapy(IMRT) by evaluation dose distribution and consequent radiobiological derived outcomes for NPC patients. Methods: Sixteen patients with NPC who used intraoral stent and 17 patients without intraoral stent were enrolled in this study. All patients underwent Helical Tomotherapy (HT) in our center. For the planning target volume (PTV), the conformity index (CI) and homogeneity index (HI) were used to compare two groups of HT plans (with or without intraoral stent). The mean dose of normal tissues were recorded for the two groups. Oral mucositis, gustatory sense, mouth opening and salivary function of each patients were weekly assessed at the beginning, during and after radiotherapy by clinical examination. Results: The mean dose metrics of oral cavity, mandible, left and right parotid gland in patients with intraoral stent was significantly decreased by 11.6%, 12.2%, 15.4%, and 8.7% on average, respectively (P &lt; 0.05), while the conformity index (CI, P = 0.056) and homogeneity index (HI, P = 0.676) of the tumor target showed no statistically different. The rates of grade I，II, III of oral mucositis of patients with intraoral stent were 43.15%, 43.75%, 12.50% when radiotherapy was just over. While the rates of patients with intraoral stent were 23.53%, 17.65%, 58.82%. There were significantly different in two groups (p = 0.022). There was no significant difference in the decline of taste function among each groups. But the symptoms of xerostomia and mouth opening restriction in the group with intraoral stent had been relieved significantly compared the group without intraoral stent at 1 month and 6 months after radiation. Conclusions: The custom-made intraoral stents showed promising value at sparing normal tissue during radiotherapy for NPC without affecting target dose coverage or tumor control. Clinical trial information: No. NJSH-2021NL-041.
Perceptions of cancer care coordination among rural patients in Hawaii.
Authors: Izumi Okado, Michelle Liu-Duerr, Tracey Hewitt, Carry Elhajj, Skyler Nishiyama, Randall F. Holcombe
Journal: Journal of Clinical Oncology (2022)

e18553 Background: Rural residents experience disproportionate burdens of cancer including higher incidence and mortality than urban residents. Disparities in rural cancer health outcomes are partially attributed to limited access to specialty care and care coordination challenges in rural areas. To date, little is known about rural cancer patients’ perceptions of care coordination (CC). In this study, we examined rural patients’ perceptions of cancer CC and compared rural and urban patients’ perceptions of cancer CC using the Care Coordination Instrument (CCI), a validated patient-report measure of CC. Methods: 80 rural patients receiving active treatment for any cancer residing in rural areas of Hawaii (Hawaii Island, Kauai) completed the CCI from Sept. 2020 to Dec. 2021. These rural areas are on separate islands from Oahu (urban) where tertiary care hospitals in Hawaii are located. Data for the urban cohorts ( n = 220) were derived from our archival data. The CCI assesses overall patients’ perceptions of CC (Total) and includes subscales that evaluate CC across three domains (Communication, Navigation, Operational). We used descriptive statistics to describe rural patients’ CC details and linear regression models to compare CCI scores between rural and urban patients. Results: Among 300 patients, demographic and clinical characteristics were similar between the rural and urban cohorts (mean age = 63.6, 56% female, most common cancer type: 28% breast and 25% GI). Patients were racially diverse, with 25% White/Caucasian, 24% Japanese, 16% Native Hawaiian, and 24% two or more race. Among rural patients, 43% indicated having traveled by air to another island (Oahu; urban) for cancer treatment (50% surgery). Of these patients, 38% indicated having paid out-of-pocket for cancer care-related travel costs. 65% of these patients reported travel costs as a burden, with 6% of patients having canceled or delayed treatment due to costs. Overall, there were no differences on the Total CCI scores between rural and urban patients ( p = 0.73). However, significant differences were found for Communication and Navigation ( p = 0.02 and p = 0.04, respectively), with rural patients reporting lower scores on these domains. No differences were found for the Operational domain scores. Conclusions: Our results demonstrate that that while rural patients’ overall perceptions of CC were similar to their urban cohorts, rural patients perceived greater CC challenges related to the communication and navigation aspects of CC. Off-island cancer care-related travel costs were reported as a significant burden for rural patients who must travel to another island for their cancer treatment. These findings highlight the need for interventions to address financial, communication and navigation challenges for rural patients in order to improve the quality of cancer care delivery in rural areas.
Landscape of tumor mutation burden and correlation to clinical outcomes in 1,744 solid cancers.
Authors: Jaeyun Jung, Sehhoon Park, Jeeyun Lee, Seung KIM
Journal: Journal of Clinical Oncology (2022)

2667 Background: Tumor mutation burden (TMB) has proven clinical utility and efficacy related to immune checkpoint inhibitor (ICI) treatment in different tumor types. However, limited data were available to understand the landscape and matched clinical outcomes to a pan-cancer extent. Methods: Target sequencing results, using TruSight Oncology 500, from 1,744 solid cancer between 2019 and 2021 as a part of real-world clinical practice were collected. Matched clinical and histological outcomes, including PD-L1 expression ( n= 798) and immunotherapy treatment ( n= 400), were analyzed. Results: Among the 33 different cancer types, high TMB was observed in 257 patients (14.7%) with a significantly higher incidence observed in carcinoma of unknown origin (33.3%), bladder cancer (32.3%), and small bowel cancer (30.0%). TMB was positively correlated with the degree of mutation in homologous recombination genes (HRD, 0.76) and microsatellite instability (MSI, 0.51). The predictive value of high TMB to ICI treatment seemed to be enhanced when it was combined with PD-L1 expression, showing higher response rates in the PD-L1 high group (63.3%) than in the low group (22.2%). In the patients with high TMB, both longer overall survival ( p = 0.015) and progression-free survival ( p = 0.020) were observed compared to the patients with low TMB. Conclusions: We examined the landscape of TMB in a different type of cancer using clinical-level target sequencing outcomes. High TMB seems to be a promising predictive biomarker of ICI, showing a positive correlation with alteration in other DNA damage response and repair-related genes and additive value to PD-L1, which needs to be validated through further prospective trials.
OTHR-18. A pilot study evaluating the access, utilization, and patient satisfaction of basic skin care products among pediatric patients prescribed medications that target the mitogen-activated protein kinase pathway
Authors: Ashley Meyer, Amy Armstrong, Andrew Cluster, Andrea Ogle, Bryan Sisk, Nicole Brossier, Mary Beck, Michele McHugh, Mohamed Abdelbaki, Carrie Coughlin
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway is dysregulated in approximately one third of all malignancies. Agents targeting this pathway are known to cause frequent and significant skin toxicity. METHODS: Patients &amp;lt;21 years of age prescribed any medication targeting the MAPK pathway within the past six months were eligible for this prospective, pilot study. Each participant received a complimentary skin care kit consisting of basic skin and oral care items. At baseline and three months after enrollment, participants completed surveys assessing demographics, skin symptoms, use of the products, and quality of life (QOL; Dermatology Life Quality Index and Child Dermatology Life Quality Index, CDLQI). OBJECTIVES: Primary aims were evaluating utilization of the kit and measuring patient satisfaction of the items included. Secondary aims included determining skin-related QOL and assessing adherence to MAPK targeted therapy. RESULTS: Eleven participants (seven male, four female; median age 13 years, range 4-21 years) have enrolled to date (enrollment goal of 30). Participant therapies included MEK inhibitors (nine), a pan-RAF inhibitor (one), and combination MEK-mTOR inhibition (one). Six have completed the three-month follow-up. Of these six, four rated their satisfaction with the kit as excellent, one each rated very good and fair satisfaction. Five participants rated the kit helpful and thought the kits should be distributed when patients begin therapy. Three started taking their targeted agent before enrolling in the study and their CDLQI changed from 3 to 0.3 (means; improved). Three participants started their targeted agent after enrollment and their CDLQI changed from 1 to 3.3 (means; worsened). CONCLUSIONS: Participants reported that skin care kits were helpful and recommended use by other patients on MAPK-targeted agents. Continued follow-up and enrollment in the study will help further explore the utility of specific products in the kits, as well as changes in patients’ QOL.
Treatment sequence for hormone receptor-positive HER2-negative advanced breast cancer: Results of a retrospective analysis of Russian patients diagnosed with aBC in 2014-2021.
Authors: Marina Stenina, Lyudmila Zhukova, Daniil Stroyakovskiy, Vera V. Karaseva, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2022)

e13032 Background: CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have dramatically changed therapeutic landscape of hormone receptor-positive HER2-negative advanced breast cancer (HR+ HER2- aBC). There are three iCDK4/6 in Russia, which are available and included into the clinical guidelines as a preferred first line treatment option beginning since 2018. The aim of this study was to assess evolution of treatment approaches to HR+ HER2- aBC and identify demographic and disease characteristics in correlation with available groups of therapy (chemotherapy, endocrine therapy ±mTOR inhibitors/ CDK4/6i). Methods: Аdult patients diagnosed with de novo or recurrent HR+ HER2- aBC in 2014-2021 identified in outpatient departments of Moscow state oncology hospitals were included into our non-interventional, descriptive, retrospective cohort study. Primary objective of this real-world study was to describe the rate of CDK4/6i usage in the first line setting. As a secondary objective, we describe patient and disease characteristics in iCDK4/6 group, as well as in the endocrine monotherapy and chemotherapy groups. Results: From the cohort of 1000 patients (full-set analysis population) 874 cases were selected, who received treatment since 2018. 45.9% (95% CI 42.6, 49.2) patients were treated with CDK4/6i in combination with endocrine therapy in the first-line setting. From them in the subgroups of patients with or without visceral metastases 50.5% (95% CI 45.5, 55.5) and 42.1% (95% CI 37.7, 46.5) were treated with CDK4/6i in the first line setting, respectively. Among 874 cases 78.0% (95% CI 75.3, 80.7) patients received endocrine therapy ± targeted therapy; in the subgroups of patients with or without visceral metastases 69.5% (95% CI 64.9, 74.1) and 84.9% (95% CI 81.7, 88.1) were treated with endocrine therapy ± targeted therapy in the first line setting, respectively. Conclusions: Endocrine therapy is a predominant therapeutic option in the first line setting for HR+ HER2- aBC. Clinical trial information: NCT04852081. [Table: see text]
Analysis of phase I clinical trials (Ph1-CT) new enrollment patterns in the immuno-oncology era.
Authors: Carlos Erasun Lecuona, Juan José Soto, Sandra Llop Serna, Nuria Mulet Margalef, Agostina Stradella, Rafael Villanueva, Mariona Calvo Campos, Maria Jove Casulleras, Carmen Cuadra Amor, Ramon Salazar Soler, Marta Gil-Martin, Marc Oliva, Juan Martin-Liberal
Journal: Journal of Clinical Oncology (2022)

e14549 Background: Immuno-Oncology (IO) has revolutionized anticancer therapeutics and changed the early drug development paradigm. Positive results and limited access to IO drugs in some countries have led to increased enrollment in IO Ph1-CT at an earlier timepoint in patients (pts) disease journey. We evaluated the impact of IO era on enrollment patterns in Ph1-CT. Methods: We retrospectively reviewed pts with recurrent/metastatic solid tumors enrolled in Ph1-CT from January 2018 to June 2021 at the Phase 1 Unit of Catalan Institute of Oncology (ICO), Barcelona, Spain. The primary goal was to assess Ph1-CT enrollment patterns, including use of molecular pre-screening/personalized drug matching, and the availability of alternative standard of care (SOC). Overall response rate (ORR) was assessed according to RECIST 1.1. Clinical benefit rate (CBR) was defined as complete/partial response+stable disease for ≥6 months. Median progression-free survival (mPFS) and overall survival (mOS) using Kaplan-Meier method were provided. Results: A total of 175 pts were enrolled in Ph1-CT. Median age was 54 years (range 43-75), Male:Female = 99:76, 99% had ECOG 0-1. The most prevalent tumors were: 32 (18%) breast, 31 (18%) colorectal, 25 (14%) urogenital and 23 (13%) glioblastoma multiforme. One hundred forty-six (83%) pts were enrolled in Ph1-CT with IO (alone or in combination) and 29 (17%) pts with targeted therapy (TT). Molecular pre-screening tests were required in 24 (14%) pts (22 pts IO vs 2 pts TT trial). Eleven (42%) pts were pre-screening failures. Screening failure (SF) rate was 19%, the main reason being clinical worsening for 7 (4%) pts. Thirty-three (19%) pts had an alternative SOC treatment available at time of enrollment. One hundred two (58%) pts had received ≤1 prior lines and 26 (89%) were IO-naïve. Finally, 129 (74%) out of 175 pts enrolled were treated within Ph1-CT. Out of 129 treated pts, ORR was achieved in 18 (14%) pts (3% complete response) and 44 (34%) had stable disease. CBR was observed in 36 (28%) pts. mPFS was 2.8 months and mOS was 10.9 months. Toxicity grade 3-4 occurred in 25 (19%) of pts and 6 (5%) pts had to interrupt treatment. Seventy-one (55%) pts received subsequent therapies: 22 (17%) in Ph1-CT; 49 (38%) SOC. Eleven (9%) pts received IO as subsequent therapy. Decline in ECOG status (baseline vs end of treatment) occurred in 65 (50%) pts. Conclusions: In our cohort of Ph1CT pts, there has been an increasing number of pts enrolled in IO trials compared to TT. Most pts received treatment within Ph1-CT at an earlier timepoint in the course of their disease (1st or 2nd lines). Our results suggest a clear impact of the IO era on the trends of Ph1-CT availability and enrollment patterns.
Circulating tumor DNA (ctDNA) mutations associate with response in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) treated with talazoparib (TALA) and temozolomide (TMZ).
Authors: Maria A Velez, Amy Lauren Cummings, Matthew C Mulroy, Edward B. Garon, Dennis J. Slamon, Jonathan W. Goldman
Journal: Journal of Clinical Oncology (2022)

8582 Background: Poly (ADP-ribose) polymerase (PARP) inhibition in combination with TMZ is a promising treatment strategy for ES-SCLC. In SCLC models, TALA, a potent PARP inhibitor, exhibits cytotoxic effects by impairing PARP proteins 1/2 and trapping PARP on DNA while TMZ potentiates antitumor response by contributing to genomic instability (Wainberg 2016). A prior analysis of ctDNA in 15 pts treated on trial with TALA and TMZ suggested that mutations in DNA damage repair (DDR) genes occurred with this combination and may associate with response (Mulroy ASCO 2021). Methods: Pts with relapsed or refractory ES-SCLC were treated with TALA 0.75 mg po daily with TMZ 37.5 mg/m2 po on days 1-5 of 28-day cycles in a phase 2 clinical trial (UCLA/TRIO-US L-07, NCT03672773). ctDNA was collected and assessed based on allele frequency and plasma copy number at baseline and every 8 weeks during treatment with the Guardant360 assay (Redwood City, CA). DDR status was defined as a mutation known or likely to result in aberrant expression of ATM or BRCA1/2 (other DDR genes not detected by assay) (Pearl 2015). Germline DDR mutations were evaluated with matched-normal (PBMC) whole exome sequencing (WES) with archival specimens by Tempus (Chicago, IL). Response to treatment was defined by RECIST 1.1 criteria. Fishers exact tests were used to compare proportions of patients, with P-values &lt;0.05 considered statistically significant ( www.r-project.org , Vienna, AU). Results: For 27 pts with evaluable response, 78 ctDNA samples were collected. The most common baseline somatic alterations were mutations in TP53 (23 pts), RB1 (8 pts), ATM (5 pts), and BRCA2 (5 pts). There were no patients with germline DDR mutations. Overall, 22/27 (81.5%) had disease control (DC), including 11 with confirmed partial responses (PR) and 11 with stable disease while 5 had progressive disease. All those with PRs and ctDNA burden &gt;0.2% at baseline experienced a ctDNA decrease at 8 weeks of treatment. DDR mutations were found in 18/27 (66.7%) pts. Of those with ≥ 1 follow-up ctDNA time point collected, 13/17 (76.4%) pts had at least one new mutation detected while on treatment, most commonly in ATM (6 pts). The appearance of new mutations associated with DC (P=0.042) and with a trend towards improved progression free survival (PFS, 5.9 m vs 3.6 m, P=0.099). All 5 pts with DDR mutations present at baseline had DC with TALA and TMZ, and 9/11 (81.8%) of those with PR had DDR mutations detected at some point during the trial, although the trend toward DC enrichment with DDR mutations did not maintain statistical significance (P=0.24). Conclusions: Mutations in DDR genes occur on treatment with TALA and TMZ and may associate with disease control. Validation in a larger cohort will be pursued.
Association of immune-related adverse events with immune-checkpoint inhibitors and treatment response in melanoma patients.
Authors: Benigno Rodriguez, José Fabián Martínez-Herrera, Lorena López Zepeda, Guillermo Olivares, Alberto Villalobos, Fernando Perez, Christian Patricio Camacho Limas, Juan Alberto Serrano, Omar Serrano Villamayor, Ervin Saúl Enciso López, Daniela Shveid Gerson, Efrain Isaias Camarin Sanchez, Diana Bonilla Molina, Juan Manuel Tovar Cabrera, Cecilia Nehmad, Juan Jose Juarez - Vignon Whaley, Raquel Gerson
Journal: Journal of Clinical Oncology (2022)

e21522 Background: Immune-related adverse effects (irAE´s) of immune-checkpoint inhibitors (ICIs) have been linked with a better treatment response in melanoma patients, especially cutaneous toxicities. However, little is known regarding other irAE´s which is important as they can be used as clinical markers of an adequate therapeutical response. Methods: We conducted a retrospective study on patients who were diagnosed with melanoma and received treatment with ICI´s between January 2015 until December 2021, immune related adverse events and their relationship with overall survival in melanoma patients treated with ICIs was the main objective of this study. Results: 53 records of patients with advance melanoma treated with ICIs between january 2016 to december 2021, demographic characteristics were as follow: 64.2% were male, mean age at diagnoses was 60.3 years, 41.5% had smoking history and 15.1% were Jewish. At diagnosis 73.6% of patients had a good functional status (ECOG 0-1). The most common histological subtypes were epithelioid (34%), and nodular (22.6%). Lung metastases was the most common affected site (49.1%), followed by brain 43.4% and non-regional nodes 42.5%. BRAF mutations was determined in 81.1% of the biopsies and 36% of them being V600E mutation. ICI´s was the preferred first line treatment in 83% of cases, median number of administered cycles were 6 (range 1-54 cycles), 60.4% of patients received pembrolizumab, 37.7% nivolumab plus ipilimumab, 20.8% nivolumab monotherapy and 5.7% ipilimumab. Throughout the studied period IrAE´s were reported in 34% of patients with 66.7% of them being grade 1-2 and 33.3% grade 3-4. The most common IrAE’s: vitiligo 38.8%, hypothyroidism22% and 3.8% pneumonitis. Median PFS at 12 months and OS was significantly better in the group of patients with irAE´s: Patients who develop an irAE´s are 7 times more likely to be disease free at 12 months and 4.1 times more likely to have a longer OS regardless of severity and type of toxicity. The impact of developing irAEs is significantly important for PFS (HR: 11.9, CI 95%: 3.28-4.71) as median PFS was not yet reached in this group. Conclusions: Development of irAEs is associated with favorable outcomes to ICIs with patients being 7 times more likely to be 12-month disease free and 4.1 times more likely to have a longer OS. irAEs can be used as clinical markers of an adequate treatment response.[Table: see text]
Pancreatic metastases after surgery for renal cell carcinoma
Authors: G. Fallara, D. Cignoli, A. Larcher, G. Rosiello, I. Rowe, F. Belladelli, G. Basile, G. Colandrea, F. De Cobelli, G. Brembilla, R. Luciano, M. Colecchia, M. Schiavo Lena, S. Partelli, S. Crippa, F. Aleotti, M. Falconi, F. Montorsi, U. Capitanio, A. Salonia
Journal: European Urology (2022)
Identification and structural analysis of novel malathion-specific DNA aptameric sensors designed for food testing
Authors: Ulhas Sopanrao Kadam, Kien Hong Trinh, Vikas Kumar, Keun Woo Lee, Yuhan Cho, Mai-Huong Thi Can, Hyebi Lee, Yujeong Kim, Sundong Kim, Jaehee Kang, Jae-Yean Kim, Woo Sik Chung, Jong Chan Hong
Journal: Biomaterials (2022)

Malathion is an organophosphate chemical (OPC) and a toxic contaminant that adversely impacts food quality, human health, biodiversity, and the environment. Due to its small size and unavailability of sensitive sensors, detection of malathion remains a challenging task. Often chromatographic methods employed to analyze OPCs suffer from several shortcomings, including cost, immobility, laboriousness, and unsuitability for point-of-care settings. Hence, developing a specific and sensitive diagnostic sensor for quick and inexpensive food testing is essential. We discovered four unique malathion-specific ssDNA aptamers; designed two independent sensing strategies using fluorescence labeling and Thioflavin T (ThT) displacement. Selected aptamers formed the G4-quadruplex-like (G4Q) structure, which helped develop a label-free detection approach with a 2.01 ppb limit of detection. Additionally, 3D structures of aptamers were generated and validated using a series of computational modeling programs. Furthermore, we explored structural features using CD spectroscopy and molecular docking, probing ligands' binding mode, and revealed vital intermolecular interactions with aptamers. Subsequently, the novel sensors were optimized to detect malathion from food samples. The novel sensors could be further developed to meet the demands of sensing and quantifying toxic contaminants from real food samples in field conditions.